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The role of subnuclear HIPK domains for the regulation of protein sumoylation

English title The role of subnuclear HIPK domains for the regulation of protein sumoylation
Applicant Schmitz M. Lienhard
Number 105365
Funding scheme Project funding (Div. I-III)
Research institution Biochemisches Institut
Institution of higher education University of Berne - BE
Main discipline Cellular Biology, Cytology
Start/End 01.10.2004 - 30.09.2007
Approved amount 181'592.00
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Keywords (3)

HIPK2; Sumo; phosphorylation

Lay Summary (English)

Lead
Lay summary
This project was started at the University of Bern and then continued for another year at the University of Giessen (Germany). The project stopped at the end of March 2007. Our results show that the polycomb group protein Pc2 binds to and colocalizes with homeodomain-interacting protein kinase (HIPK). Further in vivo and in vitro data showed that Pc2 serves as a SUMO E3 ligase for HIPK2. DNA damage-induced HIPK2 directly phosphorylates Pc2 at multiple sites which in turn controls Pc2 sumoylation and intranuclear localization. Inducible phos-phorylation of Pc2 at threonine 495 is required for its function as a E3 ligase. A non-phosporylatable Pc2 mutant does not function as a E3 ligase for HIPK2. Inducible Pc2 phos-phorylation by HIPK2 occurs in response to DNA damage, leading to increased HIPK2 sumoyla-tion. The sumoylated form of HIPK2 is much more potent in its ability to repress gene expres-sion, thereby establishing an autoregulatory feedback loop between a SUMO substrate and its cognate E3 ligase. Chromatin Immunoprecipitation experiments revealed the occurrence of HIPK2 and also Pc2 at the promoter of the cyp1b1 (cytochrome P450, family 1, subfamily B, polypeptide 1) gene which is repressed by polycomb bodies. Two new HIPK2 interactors were identified in a Y2H screen and are currently characterized for their function.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
66794 Regulation of NF-kappa B transactivation by modulatory phospho- rylations of the DNA-binding subunits during T-cell activation 01.05.2002 Project funding (Div. I-III)

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